Pulse pressure is an important characteristic of the blood pressure experienced by the arteries. As a person ages pulse pressure increases, which is a strong indicator of coronary heart disease and congestive heart failure. Conversely, pulse pressure decreases with the use of axial flow left ventricular assist devices and cardiopulmonary bypass machines, which have been shown to alter systemic vascular behavior. Additionally, changes in cyclic stretch alter vascular smooth muscle cell structure and function. These changes suggest an interaction between pulse pressure and artery structure and function, which it is important to understand. The goal of this research is to elucidate the early effects of changes in pulse pressure on arterial function, vascular cell function, and ECM composition. We use an organ culture model which allows us to examine the intact artery and the effect of pulse pressure independently of flow rate or mean pressure. This project will test the hypothesis that an increased or decreased pulse pressure will change the vasomotorfunction, cellular function, and ECM composition of the artery. The specific aims for this project are: 1) to determine how pulse amplitude affects artery function by examining vasomotor function, arterial compliance, and wall permeability, 2) to determine how pulse amplitude affects cell function by examining cell proliferation, death, VSMC phenotype, and caveolin-1 levels, and 3) to determine the effect of pulse pressure on extracellular matrix production and maintenance by examining the concentrations and distributions of MMP-2, MMP-9, collagen (I and III), and elastin. By examining artery structure and function at three different levels (whole tissue, cellular response, and ECM structure) it will be possible to elucidate the process by which these changes occur. PUBLIC HEALTH RELEVANCE: The long term goal of this research is to understand how the artery begins to remodel after exposure to a change in pulse pressure, which will improve our understanding of vascular pathophysiology and provide useful guidance for the design of heart pumps and vascular bioreactors. Ultimately this knowledge will improve vascular disease treatment.